The objective of this project is to investigate the mechanism of estrogen-induced tumorigenesis in the renal adenocarcinoma of the hamster and to compare the metabolic properties of normal kidney and tumor tissues in hamster and human. A search is being made for better methods for the diagnosis, evaluation and treatment of human renal cell cancer. In the kidney of the male hamster which develops carcinoma during prolonged administration of estrogens we have detected an estrogen receptor protein which appears to play an important role in renal tumorigenesis. Further studies have indicated that there are comparable receptors for progestins and androgens and we are studying the mechanism by which progesterone inhibits the development of experimental cancer in the hamster. We plan to test the effects of long-term implants of antiestrogens to determine whether they will block tumor induction by diethylstilbesterol. A further question under investigation is whether estradiol or diethylstilbesterol itself or a metabolite of the estrogen is the active factor in inducing tumorigenesis. Finally, we are planning to determine whether the renal tumor produces a spectrum of polyadenylic acid rich messenger RNAs, which differs from those produced by normal kidney cells; that is, does the transformation of normal kidney to the tumor condition involve a change in the pattern of transcription? Is the estrogen taken into the nucleus of the kidney cells by the receptor and there interact with the chromatin so as to change the pattern of transcription and lead to the tumor state and an altered pattern of enzymes?